NF-κB directly mediates epigenetic deregulation of common microRNAs in Epstein-Barr virus-mediated transformation of B-cells and in lymphomas

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  • dc.contributor.author Vento-Tormo, Roser
  • dc.contributor.author Rodríguez Ubreva, Javier
  • dc.contributor.author Di Lisio, Lorena
  • dc.contributor.author Islam, Abul, 1978-
  • dc.contributor.author Urquiza, José M.
  • dc.contributor.author Hernando, Henar
  • dc.contributor.author López Bigas, Núria
  • dc.contributor.author Shannon Lowe, Claire
  • dc.contributor.author Martínez, Nerea
  • dc.contributor.author Montes-Moreno, Santiago
  • dc.contributor.author Piris, Miguel A.
  • dc.contributor.author Ballestar, Esteban
  • dc.date.accessioned 2025-01-21T07:40:17Z
  • dc.date.available 2025-01-21T07:40:17Z
  • dc.date.issued 2014
  • dc.description.abstract MicroRNAs (miRNAs) have negative effects on gene expression and are major players in cell function in normal and pathological conditions. Epstein-Barr virus (EBV) infection of resting B lymphocytes results in their growth transformation and associates with different B cell lymphomas. EBV-mediated B cell transformation involves large changes in gene expression, including cellular miRNAs. We performed miRNA expression analysis in growth transformation of EBV-infected B cells. We observed predominant downregulation of miRNAs and upregulation of a few miRNAs. We observed similar profiles of miRNA expression in B cells stimulated with CD40L/IL-4, and those infected with EBNA-2- and LMP-1-deficient EBV particles, suggesting the implication of the NF-kB pathway, common to all four situations. In fact, the NF-kB subunit p65 associates with the transcription start site (TSS) of both upregulated and downregulated miRNAs following EBV infection This occurs together with changes at histone H3K27me3 and histone H3K4me3. Inhibition of the NF-kB pathway impairs changes in miRNA expression, NF-kB binding and changes at the above histone modifications near the TSS of these miRNA genes. Changes in expression of these miRNAs also occurred in diffuse large B cell lymphomas (DLBCL), which are strongly NF-kB dependent. Our results highlight the relevance of the NF-kB pathway in epigenetically mediated miRNA control in B cell transformation and DLBCL.en
  • dc.description.sponsorship Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2011-29635]; Fundación Ramón Areces [CIVP16A1834]; Catalan Agency for Management of University and Research Grants (AGAUR) [2009SGR184]; STATegra project [EU FP7 306000]. RTICC [RD06/0020/0107 to L.D.L.]. Funding for open access charge: Spanish Ministry ofEconomy and Competitiveness (MINECO) [SAF2011-29635].en
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Vento-Tormo R, Rodríguez-Ubreva J, Lisio LD, Islam ABMMK, Urquiza JM, Hernando H, et al. NF-κB directly mediates epigenetic deregulation of common microRNAs in Epstein-Barr virus-mediated transformation of B-cells and in lymphomas. Nucleic Acids Res. 2014 Sep 29;42(17):11025-39. DOI: 10.1093/nar/gku826
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gku826
  • dc.identifier.issn 0305-1048
  • dc.identifier.uri http://hdl.handle.net/10230/69215
  • dc.language.iso eng
  • dc.publisher Oxford University Press
  • dc.relation.ispartof Nucleic Acids Research. 2014 Sep 29;42(17):11025-39
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-29635
  • dc.rights © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Burkitt, Limfoma deca
  • dc.subject.other Hodgkin, Malaltia deca
  • dc.subject.other Limfomesca
  • dc.title NF-κB directly mediates epigenetic deregulation of common microRNAs in Epstein-Barr virus-mediated transformation of B-cells and in lymphomasen
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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